Dog as model for down-expression of E-cadherin and beta-catenin in tubular epithelial cells in renal fibrosis.
Mechanism of renal fibrosis leading to end stage kidney remains still a challenge of interest in humans. The pathogenesis of chronic kidney disease is characterized by progressive loss of kidney function and fibrosis. The mechanism of epithelial-mesenchymal transition (EMT) has been predominantly studied in in vitro studies, and we previously demonstrated the EMT of tubular epithelial cells in dogs. In this study, we examined and quantified the modifications of cadherin-catenin complex by immunohistochemistry of E-cadherin and beta-catenin and the mesenchymal marker vimentin in 25 dogs with three different spontaneous inflammatory renal diseases. Results showed a significant down-expression of levels of E-cadherin and beta-catenin directly correlated with the tubular-interstitial damage (TID). In TID grades 2 and 3, E-cadherin expression was significantly reduced (p < 0.001). beta-catenin expression was overall similar to E-cadherin. The mesenchymal-associated protein, vimentin, was de novo identified in tubules within areas of inflammation. In this work, we identified the loss of cadherin or catenin expression as a progressive mechanism in tubulo-interstitial fibrosis, which allows dissociation of structural integrity of renal epithelia and loss of epithelial polarity. The dog might result more significant as model for new therapies.
Aresu
Luca
L
Dipartimento di Sanità Pubblica, Patologia Comparata e Igiene Veterinaria, Facoltà di Medicina Veterinaria, Università degli Studi di Padova, Agripolis, Padova, Italy. luca.aresu@unito.it
Rastaldi
Maria Pia
MP
Pregel
Paola
P
Valenza
Federico
F
Radaelli
Enrico
E
Scanziani
Eugenio
E
Castagnaro
Massimo
M
D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D004195:Disease Models, Animal; D004285:Dogs; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D014746:Vimentin / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; D014746:Vimentin; D051176:beta Catenin